An evaluation of quinolone prescribing in a group of acute hospitals:Development of an objective measure of usage

Objectives: To develop an objective measure to enable hospital Trusts to compare their use of antibiotics. Design: Self-completion, postal questionnaire with telephone follow up. Sample: 4 hospital trusts in the English Midlands. Results: The survey showed that it was possible to collect data concerning the number of Defined Daily Doses (DDD's) of quinolone antibiotic dispensed per Finished Consultant Episode (FCE) in each Trust.. In the 4 trusts studied the mean DDD/FCE was 0.197 (range 0.117 to 0.258). This indicates that based on a typical course length of 5 days, 3.9% of patient episodes resulted in the prescription of a quinolone antibiotic. Antibiotic prescribing control measures in each Trust were found to be comparable. Conclusion: The measure will enable Trusts to objectively compare their usage of quinolone antibiotics and use this information to carry out clinical audit should differences be recorded. This is likely to be applicable to other groups of antibiotics.

Coalescence of secondary dispersions in packed beds

A study has been made of the coalescence of secondary dispersions in beds of monosized glass ballotini. The variables investigated were superficial velocity, bed depth, ballotini size and dispersed phase concentration. Equipment was designed to generate a toluene ln water dispersion with phase ratios from 0.1 - 1.0 v/v % and whose mean drop size was determined using a Coulter Counter. The coalesced drops were sized by photography and the mean diameter of the effluent drops was determined using a Malvern Particle Size Analyser. Previous models describing single phase flow in porous media are reviewed and it was found that the experimental data obtained in this study is best represented by the Carman-Kozeny equations. Relative permeability correlations were used to predict the saturation profiles across the bed from measured two phase pressure drop data. Theoretical comparison of drop capture mechanisms indicated that direct and indirect interception are predominant. The total capture efficiency for the bed can also be evaluated using Spielman and Fitzpatrick's correlation.The resulting equation is used to predict the initial, local drop capture rate in a coalescer. A mathematical description of the saturation profiles is formulated and verified by the saturation profiles obtained by relative permeability. Based on the Carman-Kozeny equation, an expression is derived analytically to .predict the two phase pressure drop using the parameters which characterise the saturation profiles. By specifying the local saturation at the inlet face for a given velocity and phase ratio, good agreement between experimental pressure drop data and the model predictions was obtained. An attempt to predict the exit drop size has been made using an analogy for flow through non cylindrical channels.

MicroRNA-155 promotes resolution of hypoxia-inducible factor 1α activity during prolonged hypoxia

The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1a (but not HIF-2a) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxiainducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1a mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1a in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1a mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1a stabilization and activity. Based on these data and a mathematical model of HIF-1a suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1a activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1a-dependent transcription. © 2011, American Society for Microbiology.

A dynamic model of the hypoxia-inducible factor 1α (HIF-1α) network

Activation of the hypoxia-inducible factor (HIF) pathway is a critical step in the transcriptional response to hypoxia. Although many of the key proteins involved have been characterised, the dynamics of their interactions in generating this response remain unclear. In the present study, we have generated a comprehensive mathematical model of the HIF-1a pathway based on core validated components and dynamic experimental data, and confirm the previously described connections within the predicted network topology. Our model confirms previous work demonstrating that the steps leading to optimal HIF-1a transcriptional activity require sequential inhibition of both prolyl- and asparaginyl-hydroxylases. We predict from our model (and confirm experimentally) that there is residual activity of the asparaginyl-hydroxylase FIH (factor inhibiting HIF) at low oxygen tension. Furthermore, silencing FIH under conditions where prolyl-hydroxylases are inhibited results in increased HIF-1a transcriptional activity, but paradoxically decreases HIF-1a stability. Using a core module of the HIF network and mathematical proof supported by experimental data, we propose that asparaginyl hydroxylation confers a degree of resistance upon HIF-1a to proteosomal degradation. Thus, through in vitro experimental data and in silico predictions, we provide a comprehensive model of the dynamic regulation of HIF-1a transcriptional activity by hydroxylases and use its predictive and adaptive properties to explain counter-intuitive biological observations.

Breakage model development and application with CFD for predicting breakage of whey protein precipitate particles

Particle breakage due to fluid flow through various geometries can have a major influence on the performance of particle/fluid processes and on the product quality characteristics of particle/fluid products. In this study, whey protein precipitate dispersions were used as a case study to investigate the effect of flow intensity and exposure time on the breakage of these precipitate particles. Computational fluid dynamic (CFD) simulations were performed to evaluate the turbulent eddy dissipation rate (TED) and associated exposure time along various flow geometries. The focus of this work is on the predictive modelling of particle breakage in particle/fluid systems. A number of breakage models were developed to relate TED and exposure time to particle breakage. The suitability of these breakage models was evaluated for their ability to predict the experimentally determined breakage of the whey protein precipitate particles. A "power-law threshold" breakage model was found to provide a satisfactory capability for predicting the breakage of the whey protein precipitate particles. The whey protein precipitate dispersions were propelled through a number of different geometries such as bends, tees and elbows, and the model accurately predicted the mean particle size attained after flow through these geometries. © 2005 Elsevier Ltd. All rights reserved.

Modelling vortex formation in an unbaffled stirred tank reactors

Agitating liquids in unbaffled stirred tank leads to the formation of a vortex in the region of the impeller shaft when operating in the turbulent flow regime. A numerical model is presented here that captures such a vortex. The volume of fluid model, a multiphase flow model was employed in conjunction with a multiple reference frame model and the shear stress turbulence model. The dimensions of the tank considered here, were 0.585 m for the liquid depth and tank diameter with a 0.2925 m diameter impeller at a height of 0.2925 m. The impeller considered was an eight-bladed paddle type agitator that was rotating with an angular velocity of 7.54 rad s (72 rpm) giving a Reynolds number of 10 and Froude number of 0.043. Preliminary results of a second investigation into the effect of liquid phase properties on the vortex formed are also presented. © 2006 Elsevier B.V. All rights reserved.

Influence of downstream processing on the breakage of whey protein precipitates

Whey proteins may be fractionated by isoelectric precipitation followed by centrifugal recovery of the precipitate phase. Transport and processing of protein precipitates may alter the precipitate particle properties, which may affect how they behave in subsequent processes. For example, the transport of precipitate solution through pumps, pipes and valves and into a centrifugal separator may cause changes in particle size and density, which may affect the performance of the separator. This work investigates the effect of fluid flow intensity, flow geometry and exposure time on the breakage of whey protein precipitates: Computational fluid dynamics (CFD) was used to quantify the flow intensity in different geometries. Flow geometry can have a critical impact on particle breakage. Sharp geometrical transitions induce large increases in turbulence that can result in substantial particle breakage. As protein precipitate particles break, they tend to form denser more compact structures. The reduction in particle size and increase in compaction is due to breakage. This makes the particles become more resistant to further breakage as particle compactness increases. The effect of flow intensity on particle breakage is coupled to exposure time, with greater exposure time producing more breakage. However, it is expected that the particles will attain an equilibrium particle size and density after prolonged exposure in a constant flow field where no further breakage will occur with exposure time. © 2005 Institution of Chemical Engineers.

Tradition versus technology:careers fairs in the 21st Century

The traditional methods of graduate recruitment do not adequately meet the needs of the changing profile of students and graduates. As industry becomes internationalized, the needs of employers are also changing. Graduate recruitment is in response to short term needs and varying levels of experience are required. A case study method was used in Dublin Institute of Technology to evaluate effectiveness of a virtual careers fair in providing greater access to job opportunities for students and graduates. Access by employers to potential employees was also measured. Findings showed that while access improved, other issues requiring attention emerged.

Effect of thermal residual stresses on fatigue crack opening and propagation behavior in an Al/SiCp metal matrix composite

The effects of a thermal residual stress field on fatigue crack growth in a silicon carbide particle-reinforced aluminum alloy have been measured. Stress fields were introduced into plates of material by means of a quench from a solution heat-treatment temperature. Measurements using neutron diffraction have shown that this introduces an approximately parabolic stress field into the plates, varying from compressive at the surfaces to tensile in the center. Long fatigue cracks were grown in specimens cut from as-quenched plates and in specimens which were given a stress-relieving overaging heat treatment prior to testing. Crack closure levels for these cracks were determined as a function of the position of the crack tip in the residual stress field, and these are shown to differ between as-quenched and stress-relieved samples. By monitoring the compliance of the specimens during fatigue cycling, the degree to which the residual stresses close the crack has been evaluated. © 1995 The Minerals, Metals & Material Society.

Majestic Gamification:a case study in the adoption of a service innovation

Purpose: A case study is presented concerning a gamified awards system designed to encourage software users to explore a suite of tools, and to share their expertise level in profile pages. Majestic is a high-tech business based in the West Midlands (UK) w hich offers a Link Intelligence database using a Software as a Service (SaaS) business model. Customers leverage the database for tasks including Search Engine Optimisation (SEO) by using a suite of web-based tools. Getting to know all the tools and how they can be deployed to good effect represents a considerable learning challenge, and Majestic were aware that. Design/methodology/approach: We present the development of Majestic Awards as a case study highlighting the most important design decisions. Then we reflect on the development process as an example of innovation adoption, thereby identifying resources and cu ltura l factors which were critical in ensuring the success of the project. Findings: The gamified awards system makes learning the tools an enjoyable, explorative experience. Success factors included identifying a clear business goal, the process/ project f it, senior management buy in, and identifying the knowledge and resources to resolve t echnical issues. Originality/value: Prior to gamification of the system, only the most expert users regu larly utilized all the tools. The user base is now more knowl edgable about the system and some users choose to use the system to publicize their expertise.